Data from amfAR's TREAT Asia Pediatric Network, composed of 16 pediatric HIV clinical centers in six countries in Southeast Asia show that 41% of their regional observational cohort of 2810 children with HIV in active follow-up is over the age of 12 years. These children are now experiencing the impact of long-term ART exposure and HIV disease, while at the same time entering into adolescence and becoming sexually active. Pilot data from Bangkok, Thailand have shown that 50% of sexually active, perinatally HIV-infected adolescent females were already infected with human papillomavirus (HPV), at a median age at sexual debut of 15 years and a current median age of 16 years. Little is known about oral or anogenital HPV infection in HIV-infected Asian male adolescents. This study will evaluate the early natural history of HPV infection and risk factors for HPV acquisition and persistence among HIV-infected and -uninfected adolescents in Asia by monitoring for cervical, vaginal, anal (female and male), oral (female and male), penile, and scrotal HPV infection, and cervical intraepithelial neoplasia.
The research aims will be accomplished through longitudinal case-control studies within a cohort of perinatally HIV-infected and matched HIV-uninfected adolescent females and males between 12-24 years of age, over 144 weeks in three participating clinical sites in Thailand and one in Vietnam. Adolescents will be sexually active and fully disclosed to if they have HIV. Annual study visits will take place at weeks 0, 48, 96, and 144;females will have additional mid-year HPV testing visits. HPV infection will be assessed in both females and males by genotyping samples from multiple body compartments, and testing for HPV 16- and HPV 18-specific neutralizing antibody, E6/E7 mRNA, and E6 oncoprotein. Vaccine eligibility will be explored by examining infection with and available antibody titers to vaccine genotypes (i.e., 6, 11, 16, 18). Assessments of sexual and other potential behavioral and biological risk behaviors will identify possible opportunities to reduce the risk of early HPV infection. Investigators will prospectively monitor for cervical squamous intraepithelial lesions and intraepithelial neoplasia with cytology testing and colposcopy-directed cervical biopsy. Detecting HPV infection in the cervix, vagina, anus, oral cavity, and male genitalia soon after sexual debut and monitoring virus clearance and cervical intraepithelial neoplasia over time will lead to a deeper understanding of HPV co-infection in the context of life-long HIV infection, and inform strategies for HPV vaccination. This study will produce the first regional-level evidence to guide HPV infection prevention and cervical intraepithelial neoplasia monitoring for perinatally HIV-infected adolescents in Asia.

Public Health Relevance

HIV-positive children in Asia are growing up into adolescence and are becoming sexually active, putting them at risk for sexually transmitted infections like human papillomavirus (HPV), the primary cause of cervical and anal cancer. Understanding how and when these adolescents acquire HPV infection can help guide infection prevention efforts and HPV vaccination strategies.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Special Emphasis Panel (ZHD1-DSR-A (52))
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Hazra, Rohan
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Foundation for AIDS Research
New York
United States
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Ananworanich, J; Prasitsuebsai, W; Kerr, S J et al. (2015) Cervical cytological abnormalities and HPV infection in perinatally HIV-infected adolescents. J Virus Erad 1:30-37